Pub Date : 2017-02-01Epub Date: 2016-12-15DOI: 10.1007/s00424-016-1916-4
Oleksandr V Povstyan, Vincenzo Barrese, Jennifer B Stott, Iain A Greenwood
Kv7.4 channels are key determinants of arterial contractility and cochlear mechanosensation that, like all Kv7 channels, have an obligatory requirement for phosphatidylinositol 4,5-bisphosphate (PIP2). βγ G proteins (Gβγ) have been identified as novel positive regulators of Kv7.4. The present study ascertained whether Gβγ increased Kv7.4 open probability through an increased sensitivity to PIP2. In HEK cells stably expressing Kv7.4, PIP2 or Gβγ increased open probability in a concentration dependent manner. Depleting PIP2 prevented any Gβγ-mediated stimulation whilst an array of Gβγ inhibitors prohibited any PIP2-induced current enhancement. A combination of PIP2 and Gβγ at sub-efficacious concentrations increased channel open probability considerably. The stimulatory effects of three Kv7.2-7.5 channel activators were also lost by PIP2 depletion or Gβγ inhibitors. This study alters substantially our understanding of the fundamental processes that dictate Kv7.4 activity, revealing a more complex and subtle paradigm where the reliance on local phosphoinositide is dictated by interaction with Gβγ.
{"title":"Synergistic interplay of Gβγ and phosphatidylinositol 4,5-bisphosphate dictates Kv7.4 channel activity.","authors":"Oleksandr V Povstyan, Vincenzo Barrese, Jennifer B Stott, Iain A Greenwood","doi":"10.1007/s00424-016-1916-4","DOIUrl":"10.1007/s00424-016-1916-4","url":null,"abstract":"<p><p>Kv7.4 channels are key determinants of arterial contractility and cochlear mechanosensation that, like all Kv7 channels, have an obligatory requirement for phosphatidylinositol 4,5-bisphosphate (PIP<sub>2</sub>). βγ G proteins (Gβγ) have been identified as novel positive regulators of Kv7.4. The present study ascertained whether Gβγ increased Kv7.4 open probability through an increased sensitivity to PIP<sub>2</sub>. In HEK cells stably expressing Kv7.4, PIP<sub>2</sub> or Gβγ increased open probability in a concentration dependent manner. Depleting PIP<sub>2</sub> prevented any Gβγ-mediated stimulation whilst an array of Gβγ inhibitors prohibited any PIP<sub>2</sub>-induced current enhancement. A combination of PIP<sub>2</sub> and Gβγ at sub-efficacious concentrations increased channel open probability considerably. The stimulatory effects of three Kv7.2-7.5 channel activators were also lost by PIP<sub>2</sub> depletion or Gβγ inhibitors. This study alters substantially our understanding of the fundamental processes that dictate Kv7.4 activity, revealing a more complex and subtle paradigm where the reliance on local phosphoinositide is dictated by interaction with Gβγ.</p>","PeriodicalId":19762,"journal":{"name":"Pflügers Archiv - European Journal of Physiology","volume":"9 1","pages":"213-223"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74231510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-26DOI: 10.1007/s00424-017-1937-7
J. Wie, SeungJoo Jeong, M. Kwak, Jongyun Myeong, M. Chae, J. K. Park, S. W. Lee, I. So
{"title":"The regulation of transient receptor potential canonical 4 (TRPC4) channel by phosphodiesterase 5 inhibitor via the cyclic guanosine 3′5′-monophosphate","authors":"J. Wie, SeungJoo Jeong, M. Kwak, Jongyun Myeong, M. Chae, J. K. Park, S. W. Lee, I. So","doi":"10.1007/s00424-017-1937-7","DOIUrl":"https://doi.org/10.1007/s00424-017-1937-7","url":null,"abstract":"","PeriodicalId":19762,"journal":{"name":"Pflügers Archiv - European Journal of Physiology","volume":"1 1","pages":"693 - 702"},"PeriodicalIF":0.0,"publicationDate":"2017-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72739176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-25DOI: 10.1007/s00424-017-1934-x
Shuai Guo, Yafei Chen, Chunli Pang, Xuzhao Wang, Jinlong Qi, Li Mo, Hai-Ling Zhang, Hailong An, Y. Zhan
{"title":"Ginsenoside Rb1, a novel activator of the TMEM16A chloride channel, augments the contraction of guinea pig ileum","authors":"Shuai Guo, Yafei Chen, Chunli Pang, Xuzhao Wang, Jinlong Qi, Li Mo, Hai-Ling Zhang, Hailong An, Y. Zhan","doi":"10.1007/s00424-017-1934-x","DOIUrl":"https://doi.org/10.1007/s00424-017-1934-x","url":null,"abstract":"","PeriodicalId":19762,"journal":{"name":"Pflügers Archiv - European Journal of Physiology","volume":"1 1","pages":"681 - 692"},"PeriodicalIF":0.0,"publicationDate":"2017-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87615257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-19DOI: 10.1007/s00424-016-1933-3
K. Sakuma, W. Aoi, A. Yamaguchi
{"title":"Molecular mechanism of sarcopenia and cachexia: recent research advances","authors":"K. Sakuma, W. Aoi, A. Yamaguchi","doi":"10.1007/s00424-016-1933-3","DOIUrl":"https://doi.org/10.1007/s00424-016-1933-3","url":null,"abstract":"","PeriodicalId":19762,"journal":{"name":"Pflügers Archiv - European Journal of Physiology","volume":"1 1","pages":"573 - 591"},"PeriodicalIF":0.0,"publicationDate":"2017-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89270586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-04DOI: 10.1007/s00424-016-1930-6
H. Hashitani, M. Nguyen, Haruka Noda, R. Mitsui, Ryuhei Higashi, K. Ohta, Kei-ichiro Nakamura, R. Lang
{"title":"Interstitial cell modulation of pyeloureteric peristalsis in the mouse renal pelvis examined using FIBSEM tomography and calcium indicators","authors":"H. Hashitani, M. Nguyen, Haruka Noda, R. Mitsui, Ryuhei Higashi, K. Ohta, Kei-ichiro Nakamura, R. Lang","doi":"10.1007/s00424-016-1930-6","DOIUrl":"https://doi.org/10.1007/s00424-016-1930-6","url":null,"abstract":"","PeriodicalId":19762,"journal":{"name":"Pflügers Archiv - European Journal of Physiology","volume":"1 1","pages":"797 - 813"},"PeriodicalIF":0.0,"publicationDate":"2017-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89714021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01Epub Date: 2016-12-03DOI: 10.1007/s00424-016-1913-7
Tanguy Corre, Eric Olinger, Sarah E Harris, Michela Traglia, Sheila Ulivi, Stefania Lenarduzzi, Hendrica Belge, Sonia Youhanna, Natsuko Tokonami, Olivier Bonny, Pascal Houillier, Ozren Polasek, Ian J Deary, John M Starr, Daniela Toniolo, Paolo Gasparini, Peter Vollenweider, Caroline Hayward, Murielle Bochud, Olivier Devuyst
The nature and importance of genetic factors regulating the differential handling of Ca2+ and Mg2+ by the renal tubule in the general population are poorly defined. We conducted a genome-wide meta-analysis of urinary magnesium-to-calcium ratio to identify associated common genetic variants. We included 9320 adults of European descent from four genetic isolates and three urban cohorts. Urinary magnesium and calcium concentrations were measured centrally in spot urine, and each study conducted linear regression analysis of urinary magnesium-to-calcium ratio on ~2.5 million single-nucleotide polymorphisms (SNPs) using an additive model. We investigated, in mouse, the renal expression profile of the top candidate gene and its variation upon changes in dietary magnesium. The genome-wide analysis evidenced a top locus (rs172639, p = 1.7 × 10-12), encompassing CLDN14, the gene coding for claudin-14, that was genome-wide significant when using urinary magnesium-to-calcium ratio, but not either one taken separately. In mouse, claudin-14 is expressed in the distal nephron segments specifically handling magnesium, and its expression is regulated by chronic changes in dietary magnesium content. A genome-wide approach identified common variants in the CLDN14 gene exerting a robust influence on the differential excretion of Mg2+ over Ca2+ in urine. These data highlight the power of urinary electrolyte ratios to unravel genetic determinants of renal tubular function. Coupled with mouse experiments, these results support a major role for claudin-14, a gene associated with kidney stones, in the differential paracellular handling of divalent cations by the renal tubule.
在一般人群中，调节肾小管对Ca2+和Mg2+处理差异的遗传因素的性质和重要性尚不清楚。我们对尿镁钙比进行了全基因组荟萃分析，以确定相关的常见遗传变异。我们纳入了来自4个遗传分离株和3个城市队列的9320名欧洲裔成年人。尿镁和钙浓度在尿样中集中测量，每项研究使用加性模型对约250万个单核苷酸多态性（snp）进行尿镁钙比的线性回归分析。我们在小鼠中研究了该候选基因的肾脏表达谱及其随膳食镁含量变化的变化。全基因组分析证实了一个顶层位点（rs172639, p = 1.7 × 10-12），包含CLDN14， CLDN14是编码claudin-14的基因，当使用尿镁钙比时，该位点在全基因组范围内显著，但单独使用任何一个位点都不显著。在小鼠中，claudin-14在处理镁的远端肾单元段表达，其表达受膳食镁含量的慢性变化调控。一种全基因组方法确定了CLDN14基因的常见变异，对尿中Mg2+与Ca2+的排泄差异产生强大的影响。这些数据强调了尿电解质比率揭示肾小管功能遗传决定因素的力量。结合小鼠实验，这些结果支持了claudin-14（一种与肾结石相关的基因）在肾小管对二价阳离子的细胞旁处理差异中的主要作用。
{"title":"Common variants in CLDN14 are associated with differential excretion of magnesium over calcium in urine.","authors":"Tanguy Corre, Eric Olinger, Sarah E Harris, Michela Traglia, Sheila Ulivi, Stefania Lenarduzzi, Hendrica Belge, Sonia Youhanna, Natsuko Tokonami, Olivier Bonny, Pascal Houillier, Ozren Polasek, Ian J Deary, John M Starr, Daniela Toniolo, Paolo Gasparini, Peter Vollenweider, Caroline Hayward, Murielle Bochud, Olivier Devuyst","doi":"10.1007/s00424-016-1913-7","DOIUrl":"10.1007/s00424-016-1913-7","url":null,"abstract":"<p><p>The nature and importance of genetic factors regulating the differential handling of Ca<sup>2+</sup> and Mg<sup>2+</sup> by the renal tubule in the general population are poorly defined. We conducted a genome-wide meta-analysis of urinary magnesium-to-calcium ratio to identify associated common genetic variants. We included 9320 adults of European descent from four genetic isolates and three urban cohorts. Urinary magnesium and calcium concentrations were measured centrally in spot urine, and each study conducted linear regression analysis of urinary magnesium-to-calcium ratio on ~2.5 million single-nucleotide polymorphisms (SNPs) using an additive model. We investigated, in mouse, the renal expression profile of the top candidate gene and its variation upon changes in dietary magnesium. The genome-wide analysis evidenced a top locus (rs172639, p = 1.7 × 10<sup>-12</sup>), encompassing CLDN14, the gene coding for claudin-14, that was genome-wide significant when using urinary magnesium-to-calcium ratio, but not either one taken separately. In mouse, claudin-14 is expressed in the distal nephron segments specifically handling magnesium, and its expression is regulated by chronic changes in dietary magnesium content. A genome-wide approach identified common variants in the CLDN14 gene exerting a robust influence on the differential excretion of Mg<sup>2+</sup> over Ca<sup>2+</sup> in urine. These data highlight the power of urinary electrolyte ratios to unravel genetic determinants of renal tubular function. Coupled with mouse experiments, these results support a major role for claudin-14, a gene associated with kidney stones, in the differential paracellular handling of divalent cations by the renal tubule.</p>","PeriodicalId":19762,"journal":{"name":"Pflügers Archiv - European Journal of Physiology","volume":"4 1","pages":"91-103"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77023462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-12-27DOI: 10.1007/s00424-016-1932-4
M. V. Tarasov, M. Bystrova, P. Kotova, O. A. Rogachevskaja, V. Sysoeva, S. Kolesnikov
{"title":"Calcium-gated K+ channels of the KCa1.1- and KCa3.1-type couple intracellular Ca2+ signals to membrane hyperpolarization in mesenchymal stromal cells from the human adipose tissue","authors":"M. V. Tarasov, M. Bystrova, P. Kotova, O. A. Rogachevskaja, V. Sysoeva, S. Kolesnikov","doi":"10.1007/s00424-016-1932-4","DOIUrl":"https://doi.org/10.1007/s00424-016-1932-4","url":null,"abstract":"","PeriodicalId":19762,"journal":{"name":"Pflügers Archiv - European Journal of Physiology","volume":"17 1","pages":"349 - 362"},"PeriodicalIF":0.0,"publicationDate":"2016-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75160749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-12-24DOI: 10.1007/s00424-016-1928-0
Agustín Asuaje, P. Smaldini, P. Martín, N. Enrique, A. Orlowski, E. A. Aiello, Carlos González Leon, G. Docena, V. Milesi
{"title":"The inhibition of voltage-gated H+ channel (HVCN1) induces acidification of leukemic Jurkat T cells promoting cell death by apoptosis","authors":"Agustín Asuaje, P. Smaldini, P. Martín, N. Enrique, A. Orlowski, E. A. Aiello, Carlos González Leon, G. Docena, V. Milesi","doi":"10.1007/s00424-016-1928-0","DOIUrl":"https://doi.org/10.1007/s00424-016-1928-0","url":null,"abstract":"","PeriodicalId":19762,"journal":{"name":"Pflügers Archiv - European Journal of Physiology","volume":"417 1","pages":"251 - 261"},"PeriodicalIF":0.0,"publicationDate":"2016-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76600913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-12-24DOI: 10.1007/s00424-016-1929-z
Guruprasad Kuntamallappanavar, Shivantika Bisen, A. Bukiya, Alex M. Dopico
{"title":"Differential distribution and functional impact of BK channel beta1 subunits across mesenteric, coronary, and different cerebral arteries of the rat","authors":"Guruprasad Kuntamallappanavar, Shivantika Bisen, A. Bukiya, Alex M. Dopico","doi":"10.1007/s00424-016-1929-z","DOIUrl":"https://doi.org/10.1007/s00424-016-1929-z","url":null,"abstract":"","PeriodicalId":19762,"journal":{"name":"Pflügers Archiv - European Journal of Physiology","volume":"15 1","pages":"263 - 277"},"PeriodicalIF":0.0,"publicationDate":"2016-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81576859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-12-21DOI: 10.1007/s00424-016-1931-5
Guangshuai Li, K. Miura, M. Kuno
{"title":"Extracellular phosphates enhance activities of voltage-gated proton channels and production of reactive oxygen species in murine osteoclast-like cells","authors":"Guangshuai Li, K. Miura, M. Kuno","doi":"10.1007/s00424-016-1931-5","DOIUrl":"https://doi.org/10.1007/s00424-016-1931-5","url":null,"abstract":"","PeriodicalId":19762,"journal":{"name":"Pflügers Archiv - European Journal of Physiology","volume":"59 1","pages":"279 - 292"},"PeriodicalIF":0.0,"publicationDate":"2016-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83913139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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